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Nat Commun. 2017 May 2;8:15162. doi: 10.1038/ncomms15162.

Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice.

Author information

1
Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
2
German Center for Cardiovascular Research (DZHK), RheinMain Oudenarder Str. 16, Berlin 13347, Germany.
3
Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Straße 15, Frankfurt 60438, Germany.
4
Department of Dermatology, University of Cologne, Kerpenerstr. 62, Cologne 50937, Germany.
5
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany.
6
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, Cologne 50931, Germany.

Abstract

MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. We use an antimiR-92a and establish a therapeutic benefit in diabetic wound healing. AntimiR-92a is modified with photolabile protecting groups, so called 'cages'. Irradiation activates intradermally injected caged antimiR-92a without substantially affecting miR-92a expression in other organs. Light activation of caged antimiR-92a improves healing in diabetic mice to a similar extent as conventional antimiRs and derepresses the miR-92a targets Itga5 and Sirt1, thereby regulating wound cell proliferation and angiogenesis. These data show that light can be used to locally activate therapeutically active antimiRs in vivo.

PMID:
28462946
PMCID:
PMC5418571
DOI:
10.1038/ncomms15162
[Indexed for MEDLINE]
Free PMC Article

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